We have examined the structure, function, development evolution, epitopes and uveitogenic site of the retinal S-antigen (48k protein). The cDNAs of S-antigen have been isolated from bovine retina libraries and their DNA sequences have been determined. The predicted amino acid sequence was matched completely with that of S-antigen determined by Edman degradation method. S-antigen polypeptide has some sequence homologies with GAlpha-transducin including the cholera toxin, pertussis toxin and enterotoxin ADP-ribosylaation sites and purine nucleotide-binding sites. S-antigen is found to be a glycoprotein and its sugar moeity is glucose and mannose. Secondary structure prediction and circular dichroism analysis indicated that S-antigen has a predominantly extended (beta-sheet) structure with a small C-terminal helical region. The location of the two monoclonal antibodies binding sites and the one uveitogenic site of S-antigen has been determined. These three linear immunogenic sites were localized within 20 amino acid residues at three separated sites. The mRNA of S-antigen is approximately 2 kb long and present in the rod cells but not present in the majority of cone cells. The majority of mRNA was found very close to the nucleus but not found in the most part of myoid and ellipoid of the rod inner segments. Also S-antigen mRNA was present in certain types of pinealocytes. S-antigen has only one gene in mouse and human, indicating that the S-antigen of retina and pineal is the same. The S-antigen genes of human and mouse were isolated and identified by partial DNA sequences and the human S-antigen gene is located on the chromosome No. 14.